US2007037783A1PendingUtilityA1
Migrastatin analogs and uses thereof
Est. expiryMar 28, 2023(expired)· nominal 20-yr term from priority
A61K 31/395A61K 31/365A61K 31/5377A61K 31/452A61K 31/496A61K 31/4025A61K 31/541A61K 31/422A61K 31/427
49
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Claims
Abstract
In one aspect, the present invention provides pharmaceutical compositions comprising a therapeutically effective amount of a compound of general formula (I), wherein R 1 —R 6 , R a—R C , Q, Y 1 , Y 2 and n are as defined herein, whereby the composition is formulated for administration to a subject at a dosage between about 0.1 mg/kg to about 50 mg/kg of body weight. In another aspect, the present invention provides a method for treating breast tumor metastasis in a subject comprising administering to a subject in need thereof a therapeutically effective amount of the inventive composition described directly above and a pharmaceutically acceptable carrier, adjuvant or vehicle.
Claims
exact text as granted — not AI-modified1 . A pharmaceutical composition comprising:
a pharmaceutically acceptable carrier, adjuvant or vehicle; and a therapeutically effective amount of a compound having the structure: or pharmaceutically acceptable salt thereof; wherein R 1 and R 2 are each independently hydrogen, halogen, —CN, —S(O) 1-2 R 1A , —NO 2 , —COR 1A , —CO 2 R 1A , —NR 1A C(═O)R 1B , —NR 1A C(═O)OR 1B , —CONR 1A R 1B , an aliphatic, heteroaliphatic, alicyclic, heteroalicyclic, aryl or heteroaryl moiety, or —WR 1A ; wherein W is independently —O—, —S— or —NR 1C —, wherein each occurrence of R 1A , R 1B and R 1C is independently hydrogen, or an aliphatic, heteroaliphatic, alicyclic, heteroalicyclic, aryl or heteroaryl moiety; or R 1 and R 2 , taken together with the carbon atoms to which they are attached, form an alicyclic, heteroalicyclic, aryl or heteroaryl moiety; R 3 is hydrogen, an aliphatic, heteroaliphatic, alicyclic, heteroalicyclic, aryl or heteroaryl moiety; or a prodrug moiety or an oxygen protecting group; R 4 is halogen, —OR 4A , —OC(═O)R 4A or —NR 4A R 4B ; wherein R 4A and R 4B are independently hydrogen, an aliphatic, heteroaliphatic, alicyclic, heteroalicyclic, aryl or heteroaryl moiety; a prodrug moiety, a nitrogen protecting group or an oxygen protecting group; or R 4A and R 4B , taken together with the nitrogen atom to which they are attached, form a heterocyclic or heteroaryl moiety; R 5 is hydrogen, an aliphatic, heteroaliphatic, alicyclic, heteroalicyclic, aryl or heteroaryl moiety; R 6 is hydrogen, halogen, —CN, —S(O) 1-2 R 6A , —NO 2 , —COR 6A , —CO 2 R 6A , —NR 6A C(═O)R 6B , —NR 6A C(═O)OR 6B , —CONR 6A R 6B , an aliphatic, heteroaliphatic, alicyclic, heteroalicyclic, aryl or heteroaryl moiety, or —WR 6A ; wherein W is independently —O—, —S— or —NR 6C , wherein each occurrence of R 6A , R 6B and R 6C is independently hydrogen, or an aliphatic, heteroaliphatic, alicyclic, heteroalicyclic, aryl or heteroaryl moiety; or R 6 and R c , taken together with the carbon atoms to which they are attached, form an alicyclic, heteroalicyclic, aryl or heteroaryl moiety; R a and each occurrence of R b are independently hydrogen, halogen, —CN, —S(O) 1-2 R a1 , —NO 2 , —COR a1 , —CO 2 R a1 , —NR a1 C(═O)R a2 , —NR a1 C(═O)OR a2 , —CONR a1 R a2 , an aliphatic, heteroaliphatic, alicyclic, heteroalicyclic, aryl or heteroaryl moiety, or —WR a1 ; wherein W is independently —O—, —S— or —NR a3 , wherein each occurrence of R a1 , R a2 and R a3 is independently hydrogen, or an aliphatic, heteroaliphatic, alicyclic, heteroalicyclic, aryl or heteroaryl moiety; or R a and the adjacent occurrence of R b , taken together with the carbon atoms to which they are attached, form an alicyclic, heteroalicyclic, aryl or heteroaryl moiety; R c is hydrogen, halogen, —CN, —S(O) 1-2 R c1 , —NO 2 , —COR c1 , —CO 2 R c1 , —NR c1 C(═O)R c2 , —NR c1 C(═O)OR c2 , —CONR c1 R c2 ; an aliphatic, heteroaliphatic, alicyclic, heteroalicyclic, aryl or heteroaryl moiety, or —WR c1 ; wherein W is independently —O—, —S— or —NR c3 —, wherein each occurrence of R c1 , R c2 and R c3 is independently hydrogen, or an aliphatic, heteroaliphatic, alicyclic, heteroalicyclic, aryl or heteroaryl moiety; or R c and R 6 , taken together with the carbon atoms to which they are attached, form an alicyclic, heteroalicyclic, aryl or heteroaryl moiety; n is an integer from 1 to 5; X 1 is O, S, NR X1 or CR X1 R X2 ; wherein R X1 and R X2 are independently hydrogen, halogen, an aliphatic, heteroaliphatic, alicyclic, heteroalicyclic, aryl or heteroaryl moiety, or a nitrogen protecting group; Q is hydrogen, halogen, —CN, —S(O) 1-2 R Q1 , —NO 2 , —COR Q1 , —CO 2 R Q1 , —NR Q1 C(═O)R Q2 , —NR Q1 C(═O)OR Q2 , —CONR Q1 R Q2 , an aliphatic, heteroaliphatic, alicyclic, heteroalicyclic, aryl or heteroaryl moiety, or —WR Q1 ; wherein W is independently —O—, —S— or —NR Q3 —, wherein each occurrence of R Q1 , R Q2 and R Q3 is independently hydrogen, or an aliphatic, heteroaliphatic, alicyclic, heteroalicyclic, aryl or heteroaryl moiety; and
Y 1 and Y 2 are independently hydrogen, an aliphatic, heteroaliphatic, alicyclic, heteroalicyclic, aryl or heteroaryl moiety; or —WR Y1 ; wherein W is independently —O—, —S— or —NR Y2 —, wherein each occurrence of R Y1 and R Y2 is independently hydrogen, or an aliphatic, heteroaliphatic, alicyclic, heteroalicyclic, aryl or heteroaryl moiety; or Y 1 and Y 2 together with the carbon atom to which they are attached form a moiety having the structure:
whereby the composition is formulated for administration to a subject at a dosage between about 0.1 mg/kg to about 50 mg/kg of body weight.
2 . The composition of claim 1 , wherein the dosage is between about 1 mg/kg to about 50 mg/kg of body weight.
3 . The composition of claim 1 , wherein the dosage is between about 0.1 mg/kg to about 40 mg/kg of body weight.
4 . The composition of claim 1 , wherein the dosage is between about 1 mg/kg to about 40 mg/kg of body weight.
5 . The composition of claim 1 , wherein the dosage is between about 0.1 mg/kg to about 30 mg/kg of body weight.
6 . The composition of claim 1 , wherein the dosage is between about 5 mg/kg to about 30 mg/kg of body weight.
7 . The composition of claim 1 , wherein the dosage is between about 1 mg/kg to about 30 mg/kg of body weight.
8 . The composition of claim 1 , wherein the dosage is between about 0.1 mg/kg to about 20 mg/kg of body weight.
9 . The composition of claim 1 , wherein the dosage is between about 1 mg/kg to about 20 mg/kg of body weight.
10 . The composition of claim 1 , wherein the dosage is 10 mg/kg or greater of body weight.
11 . The composition of claim 1 , wherein:
R 1 and R 2 are each independently hydrogen or substituted or unsubstituted lower alkyl; or R 1 and R 2 , taken together with the carbon atoms to which they are attached, form an epoxide, an aziridine or a substituted or unsubstituted cyclopropyl moiety; R 3 is hydrogen, or substituted or unsubstituted lower alkyl or aryl; a prodrug moiety or an oxygen protecting group; R 4 is halogen, —OR 4A , —OC(═O)R 4A or —NR 4A R 4B ; wherein R 4A and R 4B are independently hydrogen, or substituted or unsubstituted lower alkyl; a prodrug moiety, a nitrogen protecting group or an oxygen protecting group; or R 4A and R 4B , taken together with the nitrogen atom to which they are attached, form a heterocyclic or heteroaryl moiety; or R 4 , taken together with the carbon atom to which it is attached forms a moiety having the structure. R 5 and R 6 are each independently hydrogen or substituted or unsubstituted lower alkyl; or R 6 and R c , taken together with the carbon atoms to which they are attached, form an epoxide, an aziridine or a substituted or unsubstituted cyclopropyl moiety; R a and each occurrence of R b are independently hydrogen, halogen, alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl moiety, or —WR a1 ; wherein W is independently —O—, —S— or —NR a3 , wherein each occurrence of R a1 , and R a3 is independently hydrogen, or an alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl moiety; or R a and the adjacent occurrence of R b , taken together, form an epoxide, an aziridine or a substituted or unsubstituted cyclopropyl moiety; R c is hydrogen, halogen, alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl moiety, or —WR c1 ; wherein W is independently —O—, —S— or —NR c3 —, wherein each occurrence of R c1 and R c3 is independently hydrogen, or an alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl moiety; or R c and R 6 , taken together with the carbon atoms to which they are attached, form an epoxide, an aziridine or a substituted or unsubstituted cyclopropyl moiety; n is an integer from 1 to 5; X 1 is O, S, NR X1 or CR X1 R X2 ; wherein R X1 and R X2 are independently hydrogen, halogen, substituted or unsubstituted alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl, or a nitrogen protecting group; Q is hydrogen, halogen, —CN, —S(O) 1-2 R Q1 , —NO 2 , —COR Q1 , —CO 2 R Q1 , —NR Q1 C(═O)R Q2 , —NR Q1 C(═O)OR Q2 , —CONR Q1 R Q2 , an aliphatic, heteroaliphatic, alicyclic, heteroalicyclic, aryl or heteroaryl moiety, or —WR Q1 ; wherein W is independently —O—, —S— or —NR Q3 —, wherein each occurrence of R Q1 , R Q2 and R Q3 is independently hydrogen, or an aliphatic, heteroaliphatic, alicyclic, heteroalicyclic, aryl or heteroaryl moiety; Y 1 and Y 2 are independently hydrogen, an alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl moiety; or —WR Y1 ; wherein W is independently —O—, —S— or —NR Y2 —, wherein each occurrence of R Y1 and R Y2 is independently hydrogen, or an alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl moiety; or Y 1 and Y 2 together with the carbon atom to which they are attached form a moiety having the structure:
12 . The composition of claim 1 , wherein R a , R b and R c are each hydrogen, and the compound has one of the following structures:
wherein R 1 —R 6 , Y 2 , X 1 , n and Q are as defined in claim 1; W is O or NH; and R Y1 is hydrogen, or an aliphatic, heteroaliphatic, alicyclic, heteroalicyclic, aryl or heteroaryl moiety.
13 . The composition of claim 1 , wherein R a , R b and R c are each hydrogen, Q is a carbonyl-containing moiety and the compound has one of the following structures:
wherein R 1 —R 6 , Y 2 , X 1 , and n are as defined in claim 1; W is O or NH; and R Y1 is hydrogen, or an aliphatic, heteroaliphatic, alicyclic, heteroalicyclic, aryl or heteroaryl moiety; R 7 is a substituted or unsubstituted lower alkyl or heteroalkyl moiety; R 8 is a substituted or unsubstituted alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl moiety; and Alk is a substituted or unsubstituted C 0-6 alkylidene or C 0-6 alkenylidene chain wherein up to two non-adjacent methylene units are independently optionally replaced by CO, CO 2 , COCO, CONR Z1 , OCONR Z1 , NR Z1 NR Z2 , NR Z1 NR Z2 CO, NR Z1 CO, NR Z1 CO 2 , NR Z1 CONR Z2 , SO, SO 2 , NR Z1 SO 2 , SO 2 NR Z1 , NR Z1 SO 2 NR Z2 , O, S, or NR Z1 ; wherein each occurrence of R Z1 and R Z2 is independently hydrogen, alkyl, heteroalkyl, aryl, heteroaryl or acyl.
14 . The composition of claim 1 , wherein R a , R b and R c are each hydrogen, n is 3 and the compound has one of the following structures:
wherein R 1 —R 6 , Y 2 , Q and X 1 are as defined in claim 1; W is O or NH; and R Y1 is hydrogen, or an aliphatic, heteroaliphatic, alicyclic, heteroalicyclic, aryl or heteroaryl moiety.
15 . The composition of claim 1 , wherein R a , R b and R c are each hydrogen, n is 3, Q is a carbonyl-containing moiety, and the compound has one of the following structures:
wherein R 1 -R 6 , X 1 and Y 2 are as defined in claim 1; W is O or NH; R Y1 is hydrogen, or an aliphatic, heteroaliphatic, alicyclic, heteroalicyclic, aryl or heteroaryl moiety; R 7 is a substituted or unsubstituted lower alkyl or heteroalkyl moiety; R 8 is a substituted or unsubstituted alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl moiety; and Alk is a substituted or unsubstituted C 0-6 alkylidene or C 0-6 alkenylidene chain wherein up to two non-adjacent methylene units are independently optionally replaced by CO, CO 2 , COCO, CONR Z1 , OCONR Z1 , NR Z1 NR Z2 , NR Z1 NR Z2 CO, NR Z1 CO, NR Z1 CO 2 , NR Z1 CONR Z2 , SO, SO 2 , NR Z1 SO 2 , SO 2 NR Z1 , NR Z1 SO 2 NR Z2 , O, S, or NR Z1 ; wherein each occurrence of R Z1 and R Z2 is independently hydrogen, alkyl, heteroalkyl, aryl, heteroaryl or acyl; and R 8 is a substituted or unsubstituted alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl moiety.
16 . The composition of claim 1 , wherein R 1 and R 2 are each hydrogen.
17 . The composition of claim 1 , wherein R 5 and R 6 are each methyl.
18 . The composition of claim 1 , wherein R 3 is lower alkyl.
19 . The composition of claim 18 , wherein R 3 is methyl.
20 . The composition of claim 1 , wherein R 4 is OH, NH 2 or halogen.
21 . The composition of claim 13 or 15 , wherein R 7 is lower alkyl.
22 . The composition of claim 21 , wherein R 7 is methyl.
23 . The composition of claim 1 , wherein Q has the structure:
wherein R 7 is a substituted or unsubstituted, linear or branched, cyclic or acyclic lower alkyl moiety; R 8 is a substituted or unsubstituted carbocyclic, heterocyclic, aryl or heteroaryl moiety; and X, Y and Z are independently a bond, —O—, —S—, —C(═O)—, —NR Z1 —, —CHOR Z1 , —CHNR Z1 R Z2 , C═S, C═N(R Y1 ) or —CH(Hal); or a substituted or unsubstituted C 0-6 alkylidene or C 0-6 alkenylidene chain wherein up to two non-adjacent methylene units are independently optionally replaced by CO, CO 2 , COCO, CONR Z1 , OCONR Z1 , NR Z1 NR Z2 , NR Z1 NR Z2 CO, NR Z1 CO, NR Z1 CO 2 , NR Z1 CONR Z2 , SO, SO 2 , NR Z1 SO 2 , SO 2 NR Z1 , NR Z1 SO 2 NR Z2 , O, S, or NR Z1 ; wherein Hal is a halogen selected from F, Cl, Br and I; and each occurrence of R Z1 and R Z2 is independently hydrogen, alkyl, heteroalkyl, aryl, heteroaryl or acyl; or R Z1 and R Z2 , taken together with the nitrogen atom to which they are attached, for a heterocyclic or heteroaryl moiety; and pharmaceutically acceptable derivatives thereof.
24 . The composition of claim 23 , wherein Q has the structure:
wherein R 7 is a substituted or unsubstituted, linear or branched, cyclic or acyclic lower alkyl moiety; R 8 is a substituted or unsubstituted carbocyclic, heterocyclic, aryl or heteroaryl moiety; and R Y is hydrogen, halogen, —OR Y1 or —NR Y1 NR Y2 ; wherein R Y1 and R Y2 are independently hydrogen, alkyl, heteroalkyl, aryl, heteroaryl or acyl, or R Y1 and R Y2 , taken together with the nitrogen atom to which they are attached, for a heterocyclic or heteroaryl moiety.
25 . The composition of claim 13 , wherein R 8 is one of:
wherein p is an integer from 0 to 5; q is 1 or 2, r is an integer from 1 to 6; each occurrence of R 8A is independently hydrogen, alkyl, heteroalkyl, aryl, heteroaryl, -(alkyl)aryl or -(alkyl)heteroaryl, —OR 8C , —SR 8 C, —N(R 8C ) 2 , —SO 2 N(R 8C ) 2 , —(C═O)N 8C ) 2 , halogen, —CN, —NO 2 , —(C═O)OR 8C , —N(R 8C )(C═O)R 8D , wherein each occurrence of R 8C and R 8D is independently hydrogen, lower alkyl, lower heteroalkyl, aryl, heteroaryl, -(alkyl)aryl or -(alkyl)heteroaryl; and each occurrence of R 8B is independently hydrogen or lower alkyl.
26 . The composition of claim 25 , wherein R 8 has the structure:
wherein R 8B is hydrogen or lower alkyl.
27 . The composition of claim 1 , wherein n is 3.
28 . The composition of claim 12 , wherein Y 1 is OR Y1 and Y 2 is lower alkyl; wherein R Y1 is hydrogen or lower alkyl.
29 . The composition of claim 28 , wherein Y 1 is OH and Y 2 is CF 3 .
30 . The composition of claim 11 wherein R a , R b and R c are each hydrogen, and the compound has one of the structures:
or pharmaceutically acceptable derivative thereof;
wherein R 3 —R 6 , n and Q are as defined in claim 1; and Y 2 and R Y1 are independently hydrogen or lower alkyl.
31 . The composition of claim 1 wherein the compound has the structure:
or pharmaceutically acceptable derivative thereof;
wherein R 3 —R 6 and Q are as defined in claim 11; and Y 2 and R Y1 are independently hydrogen or lower alkyl.
32 . The composition of claim 11 wherein the compound has the structure:
or pharmaceutically acceptable derivative thereof;
wherein R 3 —R 6 and n are as defined in claim 11; Y 2 and R Y1 are independently hydrogen or lower alkyl; R 7 is a substituted or unsubstituted, linear or branched, cyclic or acyclic lower alkyl moiety; R 8B is hydrogen or lower alkyl; and X, Y and Z are independently a bond, —O—, —S—, —C(═O)—, —NR Z1 —, —CHOR Z1 , —CHNR Z1 R Z2 , C═S, C═N(R Y1 ) or —CH(Hal); or a substituted or unsubstituted C 0-6 alkylidene or C 0-6 alkenylidene chain wherein up to two non-adjacent methylene units are independently optionally replaced by CO, CO 2 , COCO, CONR Z1 , OCONR Z1 , NR Z1 NR Z2 , NR Z1 NR Z2 CO, NR Z1 CO, NR Z1 CO 2 , NR Z1 CONR Z2 , SO, SO 2 , NR Z1 SO 2 , SO 2 NR Z1 , NR Z1 SO 2 NR Z2 , O, S, or NR Z1 ; wherein Hal is a halogen selected from F, Cl, Br and I; and each occurrence of R Z1 and R Z2 is independently hydrogen, alkyl, heteroalkyl, aryl, heteroaryl or acyl; or R Z1 and R Z2 , taken together with the nitrogen atom to which they are attached, for a heterocyclic or heteroaryl moiety.
33 . The composition of claim 11 wherein the compound has the structure:
or pharmaceutically acceptable derivative thereof;
wherein R 3 —R 6 are as defined in claim 11; Y 2 and R Y1 are independently hydrogen or lower alkyl; R 7 is a substituted or unsubstituted, linear or branched, cyclic or acyclic lower alkyl moiety; R 8B is hydrogen or lower alkyl; and X, Y and Z are independently a bond, —O—, —S—, —C(═O)—, —NR Z1 —, —CHOR Z1 , —CHNR Z1 R Z2 , C═S, C═N(R Y1 ) or —CH(Hal); or a substituted or unsubstituted C 0-6 alkylidene or C 0-6 alkenylidene chain wherein up to two non-adjacent methylene units are independently optionally replaced by CO, CO 2 , COCO, CONR Z1 , OCONR Z1 , NR Z1 NR Z2 , NR Z1 NR Z2 CO, NR Z1 CO, NR Z1 CO 2 , NR Z1 CONR Z2 , SO, SO 2 , NR Z1 SO 2 , SO 2 NR Z1 , NR Z1 SO 2 NR Z2 , O, S, or NR Z1 ; wherein Hal is a halogen selected from F, Cl, Br and I; and each occurrence of R Z1 and R Z2 is independently hydrogen, alkyl, heteroalkyl, aryl, heteroaryl or acyl; or R Z1 and R Z2 , taken together with the nitrogen atom to which they are attached, for a heterocyclic or heteroaryl moiety.
34 . The composition of claim 32 or 33 , wherein —X—Y-Z together represents the moiety —CH 2 —Y—CH 2 —; wherein Y is —CHOR Y1 , —CHNR Y1 R Y2 , C═O, C═S, C═N(R Y1 ) or —CH(Hal); wherein Hal is a halogen selected from F, Cl, Br and I; and R Y1 and R Y2 are independently hydrogen, alkyl, heteroalkyl, aryl, heteroaryl or acyl, or R Y1 and R Y2 , taken together with the nitrogen atom to which they are attached, for a heterocyclic or heteroaryl moiety.
35 . The composition of claim 11 wherein the compound has the structure:
wherein R 3 —R 6 and n are as defined in claim 11; Y 2 and R Y1 are independently hydrogen or lower alkyl; R 7 is a substituted or unsubstituted, linear or branched, cyclic or acyclic lower alkyl moiety; R 8B is hydrogen or lower alkyl; and Y is —CHOR Y1 , —CHNR Y1 R Y2 , C═O, C═S, C═N(R Y1 ) or —CH(Hal); wherein Hal is a halogen selected from F, Cl, Br and I; and R Y1 and R Y2 are independently hydrogen, alkyl, heteroalkyl, aryl, heteroaryl or acyl, or R Y1 and R Y2 , taken together with the nitrogen atom to which they are attached, for a heterocyclic or heteroaryl moiety.
36 . The composition of claim 11 wherein the compound has the structure:
wherein R 3 —R 6 are as defined in claim 11; Y 2 and R Y1 are independently hydrogen or lower alkyl; R 7 is a substituted or unsubstituted, linear or branched, cyclic or acyclic lower alkyl moiety; R 8B is hydrogen or lower alkyl; and Y is —CHOR Y1 , —CHNR Y1 R Y2 , C═O, C═S, C═N(R Y1 ) or —CH(Hal); wherein Hal is a halogen selected from F, Cl, Br and I; and R Y1 and R Y2 are independently hydrogen, alkyl, heteroalkyl, aryl, heteroaryl or acyl, or R Y1 and R Y2 , taken together with the nitrogen atom to which they are attached, for a heterocyclic or heteroaryl moiety.
37 . The composition of claim 11 wherein the compound has the structure:
wherein n, R 3 and R 4 are as defined in claim 11; Y 2 and R Y1 are independently hydrogen or lower alkyl; R 8B is hydrogen or lower alkyl; and R Y is hydrogen, halogen, —OR Y1 or —NR Y1 NR Y2 ; wherein R Y1 and R Y2 are independently hydrogen, alkyl, heteroalkyl, aryl, heteroaryl or acyl, or R Y1 and R Y2 , taken together with the nitrogen atom to which they are attached, for a heterocyclic or heteroaryl moiety.
38 . The composition of claim 11 wherein the compound has the structure:
wherein R 3 and R 4 are defined as claim 11; Y 2 and R Y1 are independently hydrogen or lower alkyl; R 8B is hydrogen or lower alkyl; and R Y is hydrogen, halogen, —OR Y1 or —NR Y1 NR Y2 ; wherein R Y1 and R Y2 are independently hydrogen, alkyl heteroalkyl, aryl, heteroaryl or acyl, or R Y1 and R Y2 , taken together with nitrogen atom to which they are attached, for a heterocyclic or heteroaryl moiety.
39 . The composition of claim 11 wherein the compound has the structure:
wherein R 3 —R 6 and n are as defined in claim 11; Y 2 and R Y1 are independently hydrogen or lower alkyl; R 7 is a substituted or unsubstituted, linear or branched, cyclic or acyclic lower alkyl moiety; and R 8B is hydrogen or lower alkyl.
40 . The composition of claim 11 wherein the compound has the structure:
wherein R 3 —R 6 are as defined in claim 11; Y 2 and R Y1 are independently hydrogen or lower alkyl; R 7 is a substituted or unsubstituted, linear or branched, cyclic or acyclic lower alkyl moiety; and R 8B is hydrogen or lower alkyl.
41 . The composition of claim 11 wherein the compound has the following structure:
or a pharmaceutically acceptable salt thereof;
wherein X 1 is CH 2 , NH or O;
Y 1 and Y 2 are independently OH, C(R Y1 ) 3 or Y 1 and Y 2 taken together with the carbon atom to which they are attached are —C═O, wherein R Y1 is halo;
R 6 is H or lower alkyl;
R 5 is H or lower alkyl;
R 4 is OH; and
R 3 is alkyl.
42 . The composition of claim 41 wherein the compound has one of the following structures:
43 . The composition of claim 1 , wherein the compound is present in an amount effective to inhibit metastasis of tumor cells.
44 . The composition of claim 1 , wherein the compound is present in an amount effective to inhibit angiogenesis.
45 . The composition of claim 1 , further comprising a cytotoxic agent.
46 . The composition of claim 45 , wherein the cytotoxic agent is an anticancer agent.
47 . The composition of claim 1 , further comprising a palliative agent.
48 . A method for treating breast tumor metastasis in a subject comprising:
administering to a subject in need thereof a therapeutically effective amount of the composition of claim 1 .
49 . The method of claim 48 , wherein the dosage is between about 1 mg/kg to about 50 mg/kg of body weight.
50 . The method of claim 48 , wherein the dosage is between about 0.1 mg/kg to about 40 mg/kg of body weight.
51 . The method of claim 48 , wherein the dosage is between about 1 mg/kg to about 40 mg/kg of body weight.
52 . The method of claim 48 , wherein the dosage is between about 0.1 mg/kg to about 30 mg/kg of body weight.
53 . The method of claim 48 , wherein the dosage is between about 1 mg/kg to about 30 mg/kg of body weight.
54 . The method of claim 48 , wherein the dosage is between about 5 mg/kg to about 30 mg/kg of body weight.
55 . The method of claim 48 , wherein the dosage is between about 0.1 mg/kg to about 20 mg/kg of body weight.
56 . The method of claim 48 , wherein the dosage is between about 1 mg/kg to about 20 mg/kg of body weight.
57 . The method of claim 48 , wherein the dosage is 10 mg/kg or greater of body weight.
58 . The method of claim 48 wherein in the composition, the compound has one of the following structures:
59 . The method of claim 58 , wherein the composition is administered at a dosage between about 10 mg/kg to about 20 mg/kg of body weight.
60 . The method of claim 48 , further comprising administering a cytotoxic agent.
61 . The method of claim 60 , wherein the cytotoxic agent is an anticancer agent.
62 . The method of claim 48 , further comprising administering a palliative agent.Join the waitlist — get patent alerts
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